Process for preparation of aryl methyl malonic acids

ABSTRACT

THIS INVENTION RELATES TO A PROCESS FOR THE PREPARATION OF AN ARYL METHYL MALONIC ACID WHICH COMPRISES CONDENSING MALONIC ACID WITH AN ARYL ALDEHYDE IN THE PRESENCE OF AN ACID CHLORIDE TO FORM AN ARYL METHYLENE MALONIC ACID, AND HYDROGENATING THE LATTER TO FORM AN ARYL METHYL MALONIC ACID.

United States Patent Ofiice 3,576,852 PROCESS FOR PREPARATION OF ARYL METHYL MALONIC ACIDS Siegfried Scheler, Wiesbaden-Schierstein, and Fritz Endermann, Wiesbaden, Germany, assignors to Kalle Aktiengesellschaft, Wiesbaden-Biebrich, Germany No Drawing. Filed Nov. 24, 1967, Ser. No. 685,280

Claims priority, application Germany, Nov. 26, 1966,

Int. Cl. C 7c 51/00 US. Cl. 260-515 7 Claims ABSTRACT OF THE DISCLOSURE This invention relates to a process for the preparation of an aryl methyl malonic acid which comprises condensing malonic acid with an aryl aldehyde in the presence of an acid chloride to form an aryl methylene malonic acid, and hydrogenating the latter to form an aryl methyl malonic acid.

It is known to prepare aryl methyl malonic acids, e.g. benzyl malonic acid, by reacting sodium malonic acid diethylester with benzyl chloride and saponifying the benzyl malonic acid diethylester thus produced by means of caustic potash solution.

This known process has serious disadvantages when used on a commercial scale. It requires the use of absolute alcohol and, in particular, of metallic sodium, so that special safety precautions and measures for the exclusion of water must be taken. Further, for isolation and purification of the benzyl malonic acid diethylester, vacuum distillation is required which causes additional expenses. The yield of benzyl malonic acid diethylester obtained by this process is very unsatisfactory and ranges from 45 to 55 percent of the theoretical. Saponification of the ester to form the benzyl malonic acid must be effected under carefully controlled reaction conditions in order to reduce to a minimum the formation of byproducts. Separation of the unsaponified benzyl malonic acid diethylester from the alkaline solution and isolation of the benzyl malonic acid from the acidified aqueous phase are also expensive and time-consuming. The yield of pure benzyl malonic acid obtained by this process, calculated on the diethyl ester, is relatively low. It ranges from 50 to 60 percent of the theoretical, so that, calculated on the malonic acid diethylester, the yield is only about 25 to 30 percent of the quantity that is possible theoretically.

Further, it already has been suggested to prepare benzyl malonic acid by saponifying either benzyl cyanoform or benzyl malonic acid dinitrile with caustic soda solution, or reducing benzoyl malonic acid diethylester to benzyl malonic acid diethylester by means of Zinc dust and glacial acetic acid and saponifying this compound with caustic potash solution. These processes also require large expenditures for technical apparatus and produce unsatisfactory yields of benzyl malonic acid.

The present invention provides a process for the preparation of aryl methyl malonic acids; in which malonic acid is condensed in the presence of an acid chloride with an aryl aldehyde to form aryl methylene malonic acid, which is then converted into aryl methyl malonic acid by hydrogenation. Because of the more advantageous method of working, hydrogenation preferably is performed catalytically.

In a preferred embodiment of the process of the invention, a dialkali metal salt of an aryl methylene malonic acids is hydrogenated, in the presence of a nickel catalyst, in an aqueous solution to form the dialkali metal salt of the corresponding aryl methyl malonic acid.

3,576,852 Patented Apr. 27, 1971 The condensation of benzaldehyde with malonic acid to form benzal malonic acid is known per se. The reaction is reversible since the water formed during the condensation process remains in the reaction equilibrium. The process for the preparation of benzal malonic acid from benzaldehyde and malonic acid, as described in the literature, produces yields between 40 and 60 percent of theoretical.

It now has been found that the condensation of aromatic aldehydes with malonic acid proceeds without significant side reactions and produces essentially higher yields of benzal malonic acids, when it is performed in a low boiling point acid chloride, e.g. thionyl chloride or acetyl chloride, by which the water formed during the condensation process is removed from the reaction equilibrium, gaseous hydrogen chloride and the respective acid being produced. Acetyl chloride is preferably used as; the acid chloride. The yields, e.g., of benzal malonic acid by this process amount to 70 to percent of the theoretical. In the case of substituted aryl methylene malonic acids, the yields are somewhat lower.

In a preferred embodiment of the new process, 1 mole of malonic acid and at least 1 mole of acetyl chloride are caused to react with at least 1 mole of aromatic aldehyde.

Hydrogenation of the aryl methyl malonic acid proceeds surprisingly smoothly and Without side reactions in the catalytic process, using the nickel and precious metal catalysts customary in the industry. When using catalysts based on nickel, alcohols, esters, ketones or cyclic ethers are used as solvents, and, in the case of precious metal catalysts based on palladium or platinum, glacial acetic acid is preferred as the solvent. At room temperature, equally good results are obtained by hydrogenation at atmospheric pressure and at superatmospheric pressure, but the latter procedure is preferred in view of the time factor.

Unexpectedly, it further has been found that the hydrogenation of the monoand dialkali metal salts; of aryl methylene malonic acid in an aqueous solution with a nickel catalyst, e.g. Raney nickel, proceeds without side reactions and almost quantitatively to the corresponding salts of aryl methyl malonic acid when the process is performed in an autoclave at a temperature between 20 and 40 C. and under increased hydrogen pressure. For isolation of the free acid, the catalyst is removed and the clear aqueous solution is stirred into concentrated hydrochloric acid.

This'method of hydrogenation proved to be exceptionally economical and time-saving clue to the use of water as the solvent and the simple method of isolating the aryl methyl malonic acid.

The compounds produced in accordance With the present invention are important intermediate products for the preparation of heat-developable diazotype materials. Furthermore, they may be used for synthesizing certain aromatic amino acids and are effective as plant growth hormones.

In the following, an example is given for the performance of the process according to the invention:

EXAMPLE At a temperature of 20 to 30 C. and while vigorously agitating, 1272 parts by Weight (12 moles) of benzaldehyde were added dropwise to a mixture of 1000 parts by Weight (9.61 moles) of commercial malonic acid and 755 parts by weight (9.61 moles) of acetyl chloride which had been prepared in a three-necked flask of 4 liters capacity equipped with a stirrer, a reflux condenser and a dropping funnel. After a short time, the reaction began with intensive heat production and lively evolution of hydrogen chloride. In the beginning, the heat of reaction was balanced by exterior cooling. With advancing reaction, the addition of benzaldehyde was adjusted in such a manner that the heat of reaction evolved was just sufficient to maintain the acetyl chloride gently boiling. After all the benzaldehyde had been added, the reaction mixture was refluxed for another 20 to 30 minutes on a water bath with stirring. A clear, yellow-brown solution was thus obtained from which the main quantity of the reaction product crystallized out after a short time, while it was still warm. After cooling to room temperature, 650 parts by weight of methylene chloride were added with agitation, the pale yellow colored crude product was drawn off, and the filter residue again washed with 650 parts by weight of methylene chloride until it was free from aldehyde.

After drying, the product thus obtained was digested for 4 to 5 minutes in 2 liters of water at 20 to 30 C. while vigorously stirring; the reaction product purified in this manner was collected by suction and air-dried at 20 to 25 C. 1357 parts by weight of crude benzal malonic acid were thus obtained, corresponding to a yield of 71.5 percent of theoretical. The product melted at l84l88 C. and, after recrystallization from water, possessed a melting point of l94-l96 C., as stated in the literature.

For catalytic hydrogenation to form benzyl malonic acid, 1344 parts by weight (7 moles) of crude benzal malonic acid (melting point 184-188 C.) were added, with cooling, to a solution of 560 parts by weight (14 moles) of NaOH in 4000 parts by weight of water, and the solution thus produced was hydrogenated in an autoclave, provided With a stirrer, in the presence of 300 parts by Weight of Raney nickel at a temperature of 25 to 30 C. and an initial hydrogen pressure of 60 atmospheres. After about 3 hours, the hydrogenation process was practically completed. For isolation of the benzyl malonic acid the catalyst was separated by filtration, the filtrate was mixed with 570 parts by weight of concentrated hydrochloric acid, and the mixture was heated on a Water bathuntil the already crystalline benzyl malonic acid was again completely dissolved. After cooling, the precipitate was drawn off by suction and air-dried at 20 to 25 C. 1325 parts by weight of pure benzyl malonic acid were obtained, corresponding to a yield of 98 percent of theoretical, calculated on the quantity of crude benzal malonic acid used. The melting point of the crude product was 4 116-l18 C., in conformity with the statements made in the literature.

The process was performed in an analogous manner with 4-methyl-benzaldehyde, 4-methoxy-benzaldehyde, and 4-chloro-benzaldehyde. Good yields of 4-methylbenzal malonic acid (melting point '2072l0 C.), 4- methyl-benzyl-malonic acid (melting point 154-157 C.); 4-methoxy-benzal malonic acid (melting point -188 C.), 4-methoxy-benzyl-malonic acid (melting point 168- 172 C.); 4-chloro-benzal malonic acid (melting point 194-198 C.), and 4-chloro-benzyl-malonic acid (melting point l37139 C.), respectively, were thus obtained.

It will be obvious to those skilled in the art that many modifications may be made within the scope of the present invention without departing from the spirit thereof, and the invention includes all such modifications.

What is claimed is:

1. A process for the preparation of an aryl methyl malonic acid which comprises condensing malonic acid with an aryl aldehyde in the presence of an acid chloride to form an aryl methylene malonic acid, and hydrogenating the latter to form an aryl methyl malonic acid.

2. A process according to claim 1 in which the aryl methylene malonic acid in the form of a monoor dialkali metal salt is hydrogenated in an aqueous solution in the presence of a nickel catalyst to form a monoor dialkali metal salt of an aryl methyl malonic acid.

3. A process according to claim 1 in which the condensation is effected in acetyl chloride.

4. A process according to claims 1 to 3 in which the aryl aldehyde is *benzaldehyde.

5. A process according to claims 1 to 3 in which the aryl aldehyde is 4-methyl-benzaldehyde.

6. A process according to claims 1 to 3 in which the aryl aldehyde is 4-methoxybenzaldehyde.

7. A process according to claims 1 to 3 in which the aryl aldehyde is 4-chloro-benzaldehyde.

. References Cited Karrer: Organic Chemistry, Elsevier, New York (1938), p. 251.

Wojcik et al.: Jour. Amer. Chem. Soc., vol. 56 (1934), pp. 2424-5.

Migrdichian: Organic Synthesis, Reinhold, New York, vol. II (1957), p. 836.

JAMES A. PATTEN, Primary Examiner 

